ABSTRACT Adeno-Associated Viral (AAV) vectors are a leading technology for the delivery of genome editing machinery. The tropism of some naturally occurring AAV serotypes has been studied in various animal models. However, these surveys are heterogenous in regards to the species studied, tissues examined, cell type resolution, timing and mode of delivery. Additionally, it is unknown how AAV transduction impacts genome editing efficiency. More comprehensive information about the tissue tropism of AAV vectors across several species is needed to accelerate therapeutic development in this area. We propose to assess the tropism and genome editing efficiency of naturally occurring, clinically relevant AAVs in mice. To maximize animal model testing capacity, while centralizing the production of AAV vectors, we have assembled a collaborative team from Baylor, JAX, and UMass. In Aim 1, we will construct a panel of twelve AAV serotypes expressing a fluorescent reporter and luciferase to assess tissue tropism. We will also generate vectors expressing Staphylococcus aureus Cas9 and guide RNAs to evaluate gene editing efficiency. In Aims 2 and 3, we propose to use molecular assays and imaging to evaluate the tissue distribution and expression from each AAV serotype. Ai9 and TLR2 fluorescent reporter allele activation will be used to evaluate the tissue specificity and efficiency AAV-based genome editing for two serotypes. At the end of this 1 year project period, we will have established an atlas of AAV tropism in the mouse, and gained insight into the relationship between AAV delivery and editing efficiency for two serotypes.